Both genetic and epigenetic mutations contribute to human cancers. Mutations in oncogenes, tumor suppressor genes, and DNA repair genes have been identified in human cancers. Epigenetic mutations such as methylation of tumor suppressor genes and DNA repair genes and loss of imprinting of IGF2 gene are also associated with cancers. The major goal of my research is to identify cancer genes and epigenetic markers for human cancers.Positional cloning and candidate cloning of cancer genes. We have generated transcript maps for regions showing loss of heterozygosity (LOH) in hepatocellular carcinoma and esophageal cancer. Mutational analysis of candidate genes in the LOH region will be carried out to identify tumor suppressor genes. We are in the process to isolate DNA repair genes that will be analyzed for the presence of mutations in tumors. In addition, altered gene expression in tumors will be analyzed by methods such as cDNA microarray and Affymetrix chip. Genome-wide search of imprinted genes. We have used transcribed single nucleotide polymorphism (SNP) to isolate several imprinted genes. We will exploit large collection of transcribed SNP to isolate imprinted genes. High throughput methods such as real-time polymerase chain reaction (PCR), Affymetrix chip, and MassSpec will be used to genotype DNA and to quantitatively analyze the allele-specific gene expression. Similarly, we will systematically isolate epigenetic markers. We will examine both the imprinted genes and epigenetic markers in tumors and their matched normal tissues and in populations with high and low risk of cancer. The alteration in imprinting will be analyzed for its association with other genetic changes such as genomic instability, mutations in cancer genes, and genotype.